Phase 1 SBIR Cloud/Subscription based, Customer-Responsive Dosimetry Tool for ?-Particle Emitters PROJECT SUMMARY Radiopharmaceutical therapy (RPT) ? the use of targeted radionuclides to deliver radiation specifically to cancer cells and their microenvironment ? is a growing area with a substantial number of large and small pharmaceuticals companies developing products in this area. The dosimetric evaluation of therapeutic radiopharmaceuticals is a key requirement. Currently available dosimetry software was developed for diagnostic imaging applications. In particular, it has not been validated for alpha-emitter radiopharmaceutical therapy which is considerably more involved. In this Phase I application we propose to develop the key software elements that will demonstrate feasibility towards a broader cloud-based Medical Internal Radiation Dose (MIRD) Committee S-value-compatible dose calculation tool. This tool will: be applicable to pre-clinical studies, be well validated, properly account for the yield and emission spectrum of daughters, and appropriately consider the different pharmacokinetics of long-lived ?-emitting daughters relative to the parent. In phase I, we focus on alpha-particle emitting RPTs. Based on client requests, this area has been identified as the area of greatest need. The specific aims for phase I are: 1. Develop a module to calculate the time-integrated activity of ?RPTs that properly accounts for the yield and differential pharmacokinetics of ?-emitting daughters. 2. Using our already existing 3D-RD platform, develop automated procedures to calculate S values for all ?-emitters being considered for ?- emitter therapy. 3. Develop a module to calculate absorbed doses for radionuclides that also include ?-particle emissions. 4. Integrate the modules of aims 1, 2 and 3 into a cloud-based dosimetry tool that can be accessed by subscription. 5. Validate the tool using data by comparison with previously calculated data sets. There is increasing interest in ?-emitter RPT (?RPT). The development of commercial software that is consistent with the S-value based MIRD methodology will be valuable in helping develop safe ?RPT. For example, Radiopharmaceutical Imaging and Dosimetry, LLC (RAPID) already has, in a little more than one year of operation, obtained 6 contracts with 3 different companies related to dosimetry of new therapeutic agents. Five of these contracts are related to alpha-particle emitters. In this Phase I proposal we are focusing on the most immediate market need, and a product that could be developed with a relatively modest investment. Completion of Phase I will demonstrate the feasibility of this concept and open the way toward a full commercial product in Phase II. The work proposed in phase I will be performed in conformity with requirements for an FDA device approval application that we project for a Phase II application.